1. Field of the Invention
The invention is related to a method of producing .alpha.-amino-acylated, aryl-substituted phosphonic-acid derivatives in optically active form with the aid of chiral, amphiphilic metal-complex catalysts by means of novel, micellar, asymmetric, catalytic hydrogenation of suitable precursors.
2. Prior Art
Methods for asymmetric, catalytic hydrogenation in the presence of amphiphilic metal-complex catalysts are known only for two-phase reactions.
Micelle-forming, chiral metal complexes are also known as catalysts in asymmetric hydrolysis reactions ((a) P. Scrimin, U. Tonellato, "Ligand Surfactants: Aggregation, Cations Binding and Transport, and Catalytic Properties" in Surfactants in Solution, vol. 11, editors K. L. Mittal and D. O. Shah, Plenum Press, New York, 1991; (b) P. Scrimin, P. Tecilla, U. Tonellato, J. Org. Chem. 1994, 59, 4194; (c) A. Bunton, P. Scrimin, P. Tecilla, J. Chem. Soc., Perkin Trans. 2 1996, 419; (d) J. Budka, F. Hampl, F. Liska, P. Scrimin, P. Tecilla, U. Tonellato, J. Mol. Cat. 1996, 104, L201).
Furthermore, a number of reactions catalyzed by chiral rhodium phosphane complexes in the presence of achiral detergents in water are known in which the formation of the micellar systems is brought about by the detergents added. Thus, in the hydrogenation of dehydroamino-acid derivatives enantioselectivities of up to 97% ee can be achieve ((a) G. Oehme, E. Paetzold, R. Selke, J. Mol. Catal. 1992, 71, L1; (b) I. Grassert, E. Paetzold, G. Oehme, Tetrahedron 1993, 49, 6605; (c) A. Kumar, G. Oehme, J. P. Roque, M. Schwarze, R. Selke, Angew. Chem. 1994, 106, 2272; (d) G. Oehme, I. Grassert, H. N. Flach, "Asymmetric Complex Catalysis in Micellar Systems" in Aqueous Organometallic Chemistry and Catalysis, editors I. T. Horvath, F. Joo, Kluwer Academic Publishers, Dordrecht, 1995, p. 245; (e) H. N. Flach, I. Grassert, G. Oehme, M. Capka, Colloid Polym. Sci. 1996, 274, 261).
It is also known that surface-active, chiral, sulfonated bisphosphanes can be used in the form of their rhodium complexes in water or water mixtures with organic solvents with moderate success with regard to the stereoselectivity and activity for the asymmetric hydrogenation of amino-acid precursors (H. Ding, B. E. Hanson, J. Bakos, Angew. Chem. 1995, 107, 1728).
It is furthermore known that chiral, .alpha.-amino-acylated phosphonic-acid derivatives can be produced by means of the asymmetric hydrogenation of appropriate dehydroprecursors in the presence of optically active rhodium-complex catalysts as well as analogous racemic compounds with known achiral catalysts, during which high reaction rates and selectivities .gtoreq.90% ee are achieved only in organic solvents (U. Schmidt, G. Oehme, H. W. Krause, Synth. Commun. 1996, 26, 777 and German patent application 195 19 983.9).
Thus, Schollkopf et al. (U. Schollkopf, I. Hoppe, A. Thiele, Liebigs Ann. Chem. 1985, 555-559) achieved optical yields of 76% ee by means of the hydrogenation of .alpha.-N-formyl-.alpha., .beta.-dehydrophosphonic-acid dimethyl esters with the known, optically active DIOP-Rh catalyst in the synthesis of AlaP. In another method (U.S. Pat. No. 5,321,153) the Z-protected .alpha.-amino-.alpha., .beta.-dehydrophosphonic-acid esters are hydrogenated with a DIPAMP-Rh- complex catalyst to the saturated compounds with optical yields of approximately 90%.
The .alpha.-amino-acylated-.alpha., .beta.-unsaturated precursors necessary in all these instances are produced according to known synthesis routes ((a) U. Schollkopf, I. Hoppe, A. Thiele, Liebigs Ann. Chem. 1985, 555-559; (b) V. S. Brovarets, K. V. Zyuz, L. N. Budnik, V. A. Solodenko, B. S. Dratsch, Zh. Obsch. Khim. 1993, 63, 1259; (c) U.S. Pat. No. 5,321,153).
In addition to racemate separations, various stoichiometric methods are known which all use optically active auxiliaries and likewise result in the production of optically active .alpha.-aminophosphonic acids ((review articles: (a) B. Dharwan, D. Redmore, Phosphorous, Sulfur and Silicon 1987, 32, 119; (b) V. P. Kukhar, V. A. Soloshonov, V. A. Solodenko, Phosphorus, Sulfur and Silicon 1994, 92, 239).